Nitric oxide and renal nerves: comparison of effects on renal circulation and sodium excretion in anesthetized rats.
An array of vasoconstrictor and vasodilator agents have the potential to control intrarenal circulation; however, their relative functional importance is unclear. We compared here the importance of nitric oxide and renal nerves in studies involving sequential blockade of nitric oxide synthesis and renal denervation. In anesthetized rats, N-nitro-L-arginine methylester (L-NAME) was used for nonselective inhibition of nitric oxide synthesis and 7-nitroindazole (7-NI) for inactivation of neuronal isoform of nitric oxide synthase (nNOS). Acute unilateral renal denervation was performed noninvasively enabling observation of rapid changes. Renal cortical and medullary blood flow was determined by laser Doppler flowmetry. L-NAME decreased medullary blood flow and cortical blood flow, by 22% to 24%, whereas after 7-NI, medullary blood flow decreased by 22% and cortical blood flow about 10% (all changes significant). In untreated rats denervation significantly increased cortical blood flow (10% to 15%) but not medullary blood flow. In rats treated with L-NAME denervation partly prevented the post-inhibitor decrease in cortical blood flow but not in medullary blood flow. After 7-NI treatment, the decrease in cortical blood flow and medullary blood flow did not occur or a partial restoration of flow was seen. The denervation natriuresis was intact under L-NAME but attenuated following 7-NI. A reduction of medullary blood flow after 7-NI, similar as after L-NAME, suggests that nitric oxide generated by nNOS is mainly responsible for adequate perfusion of the medulla whereas activity of nNOS and other isoform(s) is required to maintain cortical blood flow. Renal denervation partly restored cortical blood flow reduced by nitric oxide blockade. For medullary blood flow, such restoration was seen only after inactivation of nNOS alone, suggesting an intrinsic interaction of this isoform and renal nerves.


Effects of artificial social stimuli on the reproductive schedule and hormone levels of yellow-eyed penguins (Megadyptes antipodes).
The effects of social stimuli on avian reproductive behaviors such as breeding schedules and courtship behaviors are well known due to numerous field studies. However, studies that have simultaneously examined the effects of social stimuli on reproductive behavior and the mediating endocrine mechanisms have been largely restricted to captive populations, which may not be representative of free-living populations. This study, conducted over two breeding seasons, aimed to simultaneously measure the effects of experimentally increasing auditory stimuli on the breeding schedule and endocrinology (levels of total androgen, estradiol, progesterone and prolactin) on free-living yellow-eyed penguins (Megadyptes antipodes). The yellow-eyed penguin is the least colonial of all penguins, nesting far apart from each other under dense vegetation, and, therefore, is presumed to experience much lower levels of social stimuli than other penguins. Egg laying was significantly more synchronous and tended to be earlier when birds were exposed to playbacks of the calls of conspecifics in 1 year of the study. We also found that levels of total androgen and estradiol of males in 1 year, and prolactin in another year, were proportionally higher among treated birds compared control birds that received no artificial auditory stimuli. These results show that even among supposedly solitary nesters, social stimuli could still play a role in influencing reproductive behavior and physiology. For the first time in free-living seabirds, we have demonstrated that behavioral responses to increased social stimuli are associated with hormonal changes.


Host response to human acellular dermal matrix transplantation in a primate model of abdominal wall repair.
Commercially available human acellular dermal matrix (HADM), AlloDerm((R)), was implanted as an interpositional graft in the abdominal wall of adult vervet monkeys. Host response to implanted HADM was evaluated and compared with a human cellular dermal matrix (HCDM) and a primate acellular dermal matrix (PADM). Clinical acceptance of the acellular grafts (HADM and PADM) and graft remodeling were evidenced by fibroblast repopulation and neoangiogenesis. A mild inflammatory response marked predominantly by macrophages and T-cells was present in both HADM and PADM during the first month but was absent by 3 months. Similarly, antibody and complement deposition into the grafts as well as in the serum was evident only at the early time points. Interleukin-6 (IL-6) or IL-10 was induced in some acellular graft-implanted monkeys at the early time points, but tumor necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma), or IL-2 was not detected over the study period. In contrast, significant inflammation was observed in HCDM-implanted animals, as evidenced by immune cell infiltration (p </= 0.0001), immunoglobulin G (IgG) binding (p < 0.001), complement (C5b) deposition (p < 0.05), TNF-alpha deposition (p < 0.001), and macrophage activation (p < 0.05). Abdominal wall repair in the vervet monkey is an immunologically relevant model to evaluate functional efficacy and host immune response to implanted biomaterials and may be predictive of clinical response and surgical outcomes in humans.


Treatment approaches for metastatic Ewing's sarcoma: a review of the literature.
The Ewing's sarcoma family of tumors (ESFT) is an aggressive group of neoplasms that represent approximately 3% of all pediatric malignancies. The overall survival rates in patients with localized disease are approaching 75%. The outcome for the 25% of patients who present with metastatic disease, however, remains poor, with long-term survival rates of less than 30%. This review will explore the natural history of ESFT including clinical presentation, molecular pathology, and high-risk features of the disease. Outcomes of metastatic treatment protocols to date will be examined as well as the rationale for current and future therapies. Nursing considerations in caring for patients with metastatic ESFT will be discussed. A case scenario will be reviewed to highlight treatment and supportive care issues in the management of the disease. Cancer therapy in general is becoming more complex; treatment approaches involve different ways of targeting tumor cells. It is crucial that nurses caring for these patients understand the rationale behind treatment strategies so that appropriate patient education and support may be given.


Birth weight, length and head circumference: Progression and impact over the outcome of patients with congenital heart disease.
There are few studies assessing the birth measures of patients with congenital heart disease (CHD). Our aim to evaluate their progression and impact over the outcome. The cases consisted of patients with CHD during their first hospitalization in a reference cardiac and pediatric intensive care unit (ICU) from Southern Brazil. Controls were composed of patients with no clinical evidence of CHD hospitalized soon after cases. The cases underwent high-resolution karyotype and fluorescence in situ hybridization (FISH) for 22q11 microdeletion. We analyzed birth weight, length and head circumference of patients of both groups. For CHD patients, we evaluated their progression and impact until hospitalization at ICU. Our sample was composed of 198 cases and controls. We observe a difference in birth weight of CHD patients only in relation to general population. There was a significant increase in children with CHD and weight below the lower limit from birth until the hospitalization at ICU, and this occurred more in those without complex CHD. Syndromic patients and with an extracardiac malformation also presented a greater difficulty to maintain not only the weight but also the length/height until the hospitalization. Individuals with weight below the lower limit at hospitalization who died had a tendency to present longer stay at ICU. Some CHD patients, especially without complex defects, and with syndromic aspect and a major extracardiac malformation, present a higher difficult to maintain their weight and growth, and, therefore, may be at risk and should be more closely monitored.


Polynesian women are also at risk for hyperuricaemia and gout because of a genetic defect in renal urate handling.
The prevalence of asymptomatic hyperuricaemia among Polynesian women (Maoris, Cook Islanders, Samoans, Tongans) was high--44%. This hyperuricaemia resulted from a reduced fractional uric acid clearance (FEur: uric acid clearance factored by creatinine clearance x 100--6.7 +/- 1.5%) compared with the FEur in healthy UK women (12.8 +/- 2.9%). This reduction in FEur was not as great as that in young UK women with familial juvenile hyperuricaemic nephropathy (FJHN: 5.1 +/- 1.5%) and was not associated with impaired renal function. The FEur in the normouricaemic Polynesians (9.7 +/- 1.9%) was also lower than that in healthy UK women (12.8 +/- 2.9%). The reduced FEur in these Polynesian women supports the hypothesis that indigenous Pacific races share a similar genetic defect in renal urate handling to that reported as the basis for the susceptibility to hyperuricaemia in Maori men. Neither alcohol nor hypertension contributed to this. This study also confirmed that, compared with their European counterparts, Polynesian women have a high purine intake and a strong tendency to obesity which increases with age. These factors, together with the reduced FEur, put them at added risk for gout. However, the reduction in FEur was not as great as that reported for the normouricaemic or asymptomatic hyperuricaemic Maori male (4.9 +/- 1.5% and 3.9 +/- 1.4%, respectively), confirming the same sex difference in renal urate handling in adult Polynesians as in caucasians.


Mental health and wellness in Canadian dental schools: Findings from a national study.
To survey the mental health and wellbeing content in the curricula, services, and activities of the 10 Canadian dental schools, and to explore the specifics of this area in the Faculty of Dentistry (FoD) at The University of British Columbia (UBC). An electronic survey consisted of four major categories: curricular activities and services, structural approaches, infrastructural approaches, and evaluation methods, was distributed to all Canadian dental schools. A situational analysis was conducted at UBC's FoD via document appraisal and key informants' exploratory interviews. Eight dental schools responded to the survey showing that didactic sessions being the pedagogical method to deliver resilience content. None of the responding schools reported formally evaluating their mental health content. Through situational analysis, a relational map that identified four major areas contributing to students' mental health at UBC's FoD was generated which includes four major aspects: (1) curricular content on mental health, (2) informal wellbeing and mental health networks, (3) protective, and (4) risk factors influencing students' mental health. As this study described the mental health and wellbeing activities, services, and curricular content across multiple Canadian dental schools, the diverse approaches each school adopted and how personal and professional aspects of students' lives being attempted to be addressed are a critical starting point to engage educators in dentistry. The situational analysis outcome, where a detailed description of the mental health situation at UBC's FoD, can be used to guide in-depth studies of the area of wellbeing at other dental schools.


Changes of mitochondrial ultrastructure and function during ageing in mice and Drosophila.
Ageing is a progressive decline of intrinsic physiological functions. We examined the impact of ageing on the ultrastructure and function of mitochondria in mouse and fruit flies (Drosophila melanogaster) by electron cryo-tomography and respirometry. We discovered distinct age-related changes in both model organisms. Mitochondrial function and ultrastructure are maintained in mouse heart, whereas subpopulations of mitochondria from mouse liver show age-related changes in membrane morphology. Subpopulations of mitochondria from young and old mouse kidney resemble those described for apoptosis. In aged flies, respiratory activity is compromised and the production of peroxide radicals is increased. In about 50% of mitochondria from old flies, the inner membrane organization breaks down. This establishes a clear link between inner membrane architecture and functional decline. Mitochondria were affected by ageing to very different extents, depending on the organism and possibly on the degree to which tissues within the same organism are protected against mitochondrial damage.


Assessment of pharmacists' opinions toward the behind-the-counter category of medications.
To determine pharmacists' opinions toward implementation of a behind-the-counter (BTC) category of medications and assess pharmacists' level of agreement with dispensing certain medications in this category. 473 licensed pharmacists from Ohio were randomly selected for inclusion in the study, 248 of whom completed the survey (52.4% response rate). A self-administered, mailed questionnaire was used to collect data on pharmacists' opinions toward a BTC category, including usefulness to patients, reimbursement issues, impact on patient care, and access issues. The researchers also assessed the degree to which pharmacists felt educationally prepared regarding a BTC category and the potential need for further training and/or education. The questionnaire also included 25 prescription drugs identified from pharmacist focus groups to evaluate appropriateness for inclusion in a BTC category. Pharmacists moderately agreed (5.78 ± 1.33 [mean ± SD]) that introducing a BTC category of medication would advance the profession's goals of providing more pharmacist-directed patient care. Pharmacists also moderately agreed (6.09 ± 1.71) that patient counseling should be mandatory before providing any medications in a BTC category. At their current practice site, pharmacists moderately agreed (5.65 ± 1.62) that they would participate in providing BTC medications; however, they felt the largest issue pertaining to a BTC category of medications was the added amount of time that would be spent with patients (5.34 ± 1.53). On the other hand, pharmacists moderately agreed (5.82 ± 1.26) that they would take the time to counsel patients on BTC medications. Prescription prenatal vitamins (1 mg folic acid), triamcinolone cream, silver sulfadiazine cream, mometasone nasal inhalation, fluconazole 150 mg, epinephrine injection, promethazine, and mebendazole were considered the most appropriate for a BTC category of medications. Ultimately, pharmacists moderately agreed that a BTC category is a change in the pharmacy profession that they were willing to embrace.


A Review of Piezoelectric Footwear Energy Harvesters: Principles, Methods, and Applications.
Over the last couple of decades, numerous piezoelectric footwear energy harvesters (PFEHs) have been reported in the literature. This paper reviews the principles, methods, and applications of PFEH technologies. First, the popular piezoelectric materials used and their properties for PEEHs are summarized. Then, the force interaction with the ground and dynamic energy distribution on the footprint as well as accelerations are analyzed and summarized to provide the baseline, constraints, potential, and limitations for PFEH design. Furthermore, the energy flow from human walking to the usable energy by the PFEHs and the methods to improve the energy conversion efficiency are presented. The energy flow is divided into four processing steps: (i) how to capture mechanical energy into a deformed footwear, (ii) how to transfer the elastic energy from a deformed shoes into piezoelectric material, (iii) how to convert elastic deformation energy of piezoelectric materials to electrical energy in the piezoelectric structure, and (iv) how to deliver the generated electric energy in piezoelectric structure to external resistive loads or electrical circuits. Moreover, the major PFEH structures and working mechanisms on how the PFEHs capture mechanical energy and convert to electrical energy from human walking are summarized. Those piezoelectric structures for capturing mechanical energy from human walking are also reviewed and classified into four categories: flat plate, curved, cantilever, and flextensional structures. The fundamentals of piezoelectric energy harvesters, the configurations and mechanisms of the PFEHs, as well as the generated power, etc., are discussed and compared. The advantages and disadvantages of typical PFEHs are addressed. The power outputs of PFEHs vary in ranging from nanowatts to tens of milliwatts. Finally, applications and future perspectives are summarized and discussed.


Chemiluminescent and bioluminescent assays as innovative prospects for mycotoxin determination in food and feed.
Mycotoxin contamination of food and feedstuffs is among the top priorities for human and animal safety. The currently used techniques for mycotoxin determination, either chromatography or ELISA, are unsuitable for routine in-field assessment. There is an urgent need for other accurate, simple and cost-effective techniques that can be used as a screening tool for a rapid estimation of mycotoxin contamination in commodity lots. This paper reviews the literature on the use of chemiluminescence (CL) and bioluminescence (BL) assays for direct or indirect mycotoxin assessment. The chemiluminescence immunoassays, adenosine triphosphate (ATP) bioluminescence and bioassays are reviewed and their advantages and limitations discussed. These techniques used in food testing and the pharmaceutical industry offer promise as rapid techniques for mycotoxin determination. Chemiluminescence and bioluminescence bioassays are the most innovative alternatives to the conventional techniques used for mycotoxin determination in food and feed.


Thioredoxin-mimetic peptides (TXM) reverse auranofin induced apoptosis and restore insulin secretion in insulinoma cells.
The thioredoxin reductase/thioredoxin system (TrxR/Trx1) plays a major role in protecting cells from oxidative stress. Disruption of the TrxR-Trx1 system keeps Trx1 in the oxidized state leading to cell death through activation of the ASK1-Trx1 apoptotic pathway. The potential mechanism and ability of tri- and tetra-oligopeptides derived from the canonical -CxxC- motif of the Trx1-active site to mimic and enhance Trx1 cellular activity was examined. The Trx mimetics peptides (TXM) protected insulinoma INS 832/13 cells from oxidative stress induced by selectively inhibiting TrxR with auranofin (AuF). TXM reversed the AuF-effects preventing apoptosis, and increasing cell-viability. The TXM peptides were effective in inhibiting AuF-induced MAPK, JNK and p38(MAPK) phosphorylation, in correlation with preventing caspase-3 cleavage and thereby PARP-1 dissociation. The ability to form a disulfide-bridge-like conformation was estimated from molecular dynamics simulations. The TXM peptides restored insulin secretion and displayed Trx1 denitrosylase activity. Their potency was 10-100-fold higher than redox reagents like NAC, AD4, or ascorbic acid. Unable to reverse ERK1/2 phosphorylation, TXM-CB3 (NAc-Cys-Pro-Cys amide) appeared to function in part, through inhibiting ASK1-Trx dissociation. These highly effective anti-apoptotic effects of Trx1 mimetic peptides exhibited in INS 832/13 cells could become valuable in treating adverse oxidative-stress related disorders such as diabetes.


Development of sequence characterized amplified genomic regions (SCAR) for fungal systematics: proof of principle using Alternaria, Ascochyta and Tilletia.
SCARs were developed by cloning RAPD-PCR amplicons into commercially available vectors, sequencing them and designing specific primers for PCR, direct sequencing and phylogenetic analysis. Eighteen to seventy percent of cloned RAPD-PCR amplicons were phylogenetically informative among closely related small-spored Alternaria spp., Ascochyta spp. and Tilletia spp., taxa that have been resistant to phylogenetic analysis with universally primed, protein-coding sequence data. Selected SCARs were sequenced for larger, population-scale samples of each taxon and demonstrated to be useful for phylogenetic inference. Variation observed in the cloned SCARs generally was higher than variation in nuclear ribosomal internal transcribed spacer (ITS) and several protein-coding sequences commonly used in lower level fungal systematics. Sequence data derived from SCARs will provide sufficient resolution to address lower level phylogenetic hypotheses in Alternaria, Ascochyta, Tilletia and possibly many other fungal groups and organisms.


Posttranscriptional repression of the cel gene of the ColE7 operon by the RNA-binding protein CsrA of Escherichia coli.
Carbon storage regulator (CsrA) is a eubacterial RNA-binding protein that acts as a global regulator of many functionally diverse chromosomal genes. Here, we reveal that CsrA represses expression from an extrachromosomal element of Escherichia coli, the lysis gene (cel) of the ColE7 operon (cea-cei-cel). This operon and colicin expression are activated upon SOS response. Disruption of csrA caused approximately 5-fold increase of the lysis protein. Gel mobility shift assays established that both the single-stranded loop of the T1 stem-loop distal to cei, and the putative CsrA binding site overlapping the Shine-Dalgarno sequence (SD) of the cel gene are important for CsrA binding. Substitution mutations at SD relieved CsrA-dependent repression of the cel gene in vivo. Steady-state levels and half-life of the cel mRNA were not affected by CsrA, implying that regulation is mediated at the translational level. Levels of CsrB and CsrC sRNAs, which bind to and antagonize CsrA, were drastically reduced upon induction of the SOS response, while the CsrA protein itself remained unaffected. Thus, CsrA is a trans-acting modulator that downregulates the expression of lysis protein, which may confer a survival advantage on colicinogenic E. coli under environment stress conditions.


Arginine 719 in human plasminogen mediates formation of the staphylokinase:plasmin activator complex.
Staphylokinase (Sak), a 16-kDa bacterial protein, forms a 1:1 stoichiometric complex with the serine proteinase domain of human plasmin, which in turn converts other plasminogen molecules into plasmin. To identify amino acid residues critical for generating the Sak:plasmin activator complex, alanine-scanning mutagenesis was performed on phage-displayed micro-plasminogen (microPlg). Substitution of Arg719 with Ala [microPlg(R719A)] disrupted complex formation, although the sensitivity of phage-displayed microPlg(R719A) to activation by urokinase and the amidolytic activity of the micro-plasmin derivative [microPli(R719A)] remained unaffected. Likewise, the soluble microPlg(R719A) molecule did not generate a functional activator complex with Sak, whereas quantitative activation into plasmin was obtained upon incubation with either urokinase or the Sak:plasmin complex. Real-time biospecific affinity measurements revealed that the Arg --> Ala substitution at position 719 increased the equilibrium dissociation constant between microPlg(R719A) and Sak from 46 nM to 1 microM, primarily by reducing the association rate constant. Arg719 has recently also been implied in the functional complex formation between human plasmin and streptokinase [Dawson, K. M., Marshall, J. M., Raper, R. H., Gilbert, R. J., and Ponting, C. P. (1994) Biochemistry 33, 12042-12047.], suggesting that both bacterial cofactors may share common structural and/or mechanistic aspects for plasminogen activation.


The role of interleukin-6 and C-reactive protein in non-thyroidal illness in premature infants followed in neonatal intensive care unit.
To investigate the role of interleukin-6 (IL-6) and C-reactive protein (CRP) in non-thyroidal illness (NTI) in premature infants. Serum levels of IL-6 and CRP, thyroid-stimulating hormone (TSH), total thyroxine (T4), free T4 (fT4), total triiodothyronine (T3), and free T3 (fT3) were determined at the 1st, 2nd and 4th weeks of postnatal life in 148 premature infants born before 33 weeks of gestation. At the 1st week, serum T3 was negatively correlated with IL-6 (r= -0.33, p= 0.001) and CRP (r= -0.17, p= 0.03). Serum T3 was negatively and more strongly correlated with IL-6 (r= -0.49, p= 0.001) and CRP (r=- 0.33, p= 0.03) at the 2nd week, at which time sepsis frequency and low T3 rates were the highest. At the 4th week, mortality rate was higher among infants with lower T3 levels. High IL-6 and CRP values related to neonatal sepsis might have a significant role in the pathogenesis of NTI in premature infants.


Detection of Chlamydia trachomatis antigen & Toxoplasma gondii (IgM) & Mycoplasma hominis (IgG) antibodies by ELISA in women with bad obstetric history.
A total of 365 non pregnant women with bad obstetrics history (BOH) were studied with a control group of 100 women who had delivered full term clinically normal infants. The presence of C. trachomatis antigen and T. gondii (IgM) and M. hominis (IgG) antibodies was assessed by ELISA test. C. trachomatis antigen was detected in 28.2 per cent of women with BOH whereas T. gondii and M. hominis specific antibodies were found in 43.83 and 27.1 per cent respectively, these were highly significant (P < 0.001) in comparison with the control group. In case, facilities for culture are not available then detection of antigen and IgM class of antibodies by ELISA can pinpoint current infection.


The effect of single doses of penbutolol and propranolol L.A. on psychomotor performance.
The effect of single oral doses of penbutolol (40 mg) and propranolol L.A. (160 mg) on psychomotor performance of 12 normal individuals has been investigated. Subjects were randomly administered penbutolol, propranolol L.A. and placebo according to a double-blind, three-part cross-over design. At 3 h post-dosing both penbutolol and propranolol L.A. significantly increased (P less than 0.001) complex reaction times when compared to placebo. By 24 h post-dosing the mean complex reaction times for penbutolol and propranolol L.A. were not significantly different from placebo.


Quorum sensing in Campylobacter jejuni: detection of a luxS encoded signalling molecule.
The expression of a wide variety of physiological functions in many bacterial species is modulated by quorum sensing, a population-dependent signalling mechanism that involves the production and detection of extracellular signalling molecules. The genome sequence of Campylobacter jejuni NCTC 11168 contains a gene encoding an orthologue of LuxS, which is required for autoinducer-2 (AI-2) production in other bacterial species, but does not contain genes predicted to encode any known acyl-homoserine lactone synthetase. This study demonstrates that C. jejuni produces functional AI-2 activity through the ability of cell-free extracts to specifically induce bioluminescence in Vibrio harveyi BB170, a reporter strain for quorum-sensing system 2. Production of this signalling compound was shown to be dependent upon the product of the C. jejuni luxS gene (Cj1198). While the luxS mutant showed comparable growth rate, resistance to oxidative stress and ability to invade Caco-2 cell monolayers to the parental strain, it exhibited decreased motility haloes in semisolid media, suggesting a role for quorum sensing in the regulation of motility.


A deep learning framework for prostate localization in cone beam CT-guided radiotherapy.
To develop a deep learning-based model for prostate planning target volume (PTV) localization on cone beam computed tomography (CBCT) to improve the workflow of CBCT-guided patient setup. A two-step task-based residual network (T2 RN) is proposed to automatically identify inherent landmarks in prostate PTV. The input to the T2 RN is the pretreatment CBCT images of the patient, and the output is the deep learning-identified landmarks in the PTV. To ensure robust PTV localization, the T2 RN model is trained by using over thousand sets of CT images with labeled landmarks, each of the CTs corresponds to a different scenario of patient position and/or anatomy distribution generated by synthetically changing the planning CT (pCT) image. The changes, including translation, rotation, and deformation, represent vast possible clinical situations of anatomy variations during a course of radiation therapy (RT). The trained patient-specific T2 RN model is tested by using 240 CBCTs from six patients. The testing CBCTs consists of 120 original CBCTs and 120 synthetic CBCTs. The synthetic CBCTs are generated by applying rotation/translation transformations to each of the original CBCT. The systematic/random setup errors between the model prediction and the reference are found to be <0.25/2.46 mm and 0.14/1.41° in translation and rotation dimensions, respectively. Pearson's correlation coefficient between model prediction and the reference is higher than 0.94 in translation and rotation dimensions. The Bland-Altman plots show good agreement between the two techniques. A novel T2 RN deep learning technique is established to localize the prostate PTV for RT patient setup. Our results show that highly accurate marker-less prostate setup is achievable by leveraging the state-of-the-art deep learning strategy.


Prodan as a membrane surface fluorescence probe: partitioning between water and phospholipid phases.
Fluorescence spectral features of 6-propionyl-2-dimethylaminonaphthalene (Prodan) in phospholipid vesicles of different phase states are investigated. Like the spectra of 6-lauroyl-2-dimethylaminonaphthalene (Laurdan), the steady-state excitation and emission spectra of Prodan are sensitive to the polarity of the environment, showing a relevant shift due to the dipolar relaxation phenomenon. Because of the different lengths of their acyl residues, the partitioning of the two probes between water and the membrane bilayer differs profoundly. To account for the contribution of Prodan fluorescence arising from water, we introduce a three-wavelength generalized polarization method that makes it possible to separate the spectral properties of Prodan in the lipid phase and in water, and to determine the probe partitioning between phospholipid and water and between the gel and the liquid-crystalline phases of phospholipids. In contrast to Laurdan, Prodan preferentially partitions in the liquid-crystalline phase with respect to the gel and is sensitive to the polar head pretransition, and its partition coefficient between the membrane and water depends on the phase state, i.e., on the packing of the bilayer. Prodan is sensitive to polarity variations occurring closer to the bilayer surface than those detected by Laurdan.


Discovery of quinazolines as histamine H4 receptor inverse agonists using a scaffold hopping approach.
From a series of small fragments that was designed to probe the histamine H(4) receptor (H(4)R), we previously described quinoxaline-containing fragments that were grown into high affinity H(4)R ligands in a process that was guided by pharmacophore modeling. With a scaffold hopping exercise and using the same in silico models, we now report the identification and optimization of a series of quinazoline-containing H(4)R compounds. This approach led to the discovery of 6-chloro-N-(furan-3-ylmethyl)2-(4-methylpiperazin-1-yl)quinazolin-4-amine (VUF10499, 54) and 6-chloro-2-(4-methylpiperazin-1-yl)-N-(thiophen-2-ylmethyl)quinazolin-4-amine (VUF10497, 55) as potent human H(4)R inverse agonists (pK(i) = 8.12 and 7.57, respectively). Interestingly, both compounds also possess considerable affinity for the human histamine H(1) receptor (H(1)R) and therefore represent a novel class of dual action H(1)R/H(4)R ligands, a profile that potentially leads to added therapeutic benefit. Compounds from this novel series of quinazolines are antagonists at the rat H(4)R and were found to possess anti-inflammatory properties in vivo in the rat.


Fine structure of the myotendinous junction and "terminal coupling" in the skeletal muscle of the lamprey, Lampetra japonica.
The myotendinous junction in the skeletal muscle of adult lamprey Lampetra japonica was studied with an electron microscope. Numerous finger-like sarcolemmal invaginations were present at the ends of muscle fibers to form the myotendinous junction. Parietal fibers of each muscle unit showed more closely distributed sarcolemmal invaginations than central fibers. Features of the myotendinous junction generally conform to the accounts in the literature. The sarcolemmal invagination was covered on its sarcoplasmic aspect by the connecting filament layer and the dense amorphous attachment layer, and on the extracellular aspect by the intermediary layer and the external lamina with collagen fibrils arising from the myosepta. Sarcolemmal invaginations were sometimes seen to consist of a pair of sarcolemmas of adjacent muscle fibers within a muscle unit, which is characteristic to the myotendinous junction of lamprey. It is noteworthy that the connecting filament layer is much thinner than that, e. g., in the tadpole tail muscles (Nakao, '74). Furthermore, it is much thicker in the parietal fibers than in the central fibers. The sarcolemma of the terminal segment of the invagination frequently showed specific coupling with cisterns of the sarcoplasmic reticulum (terminal coupling). The external lamina is partially or completely deficient in the terminal segment of sarcolemmal invaginations which form terminal couplings so that collagen fibrils contained in the invagination appear to be in direct contact with the sarcolemma; however, definite relationships of collagen fibrils with the sarcolemma and the external lamina in the terminal segment of invagination still remain obscure. This type of coupling is considered to play a role in the coupling of excitation to contraction of muscle fibers as triads and diads.


Microscopic evidence of a new 9R-AgI polytype heterostructure.
The extraordinary high ionic conductivity and the phase transition with large thermal hysteresis of AgI:Al2O3 nanocomposites can be ascribed to the presence of unusual polytype 7H and 9R modification of AgI as mesoscopic heterostructures. In addition to the 7H AgI phase in the composites previously identified by a Rietveld analysis of X-ray diffraction, a new 9R AgI polytype with a characteristic three-fold contrast was directly evidenced by high resolution transmission electron microscopy. The epitaxial intergrowth of various polytypes was also microscopically evidenced which is in accordance with the Rietveld analysis.


Deep neuromuscular block to optimize surgical space conditions during laparoscopic surgery: a systematic review and meta-analysis.
Neuromuscular block (NMB) is frequently used in abdominal surgery to improve surgical conditions by relaxation of the abdominal wall and prevention of sudden muscle contractions. The evidence supporting routine use of deep NMB is still under debate. We aimed to provide evidence for the superiority of routine use of deep NMB during laparoscopic surgery. We performed a systematic review and meta-analysis of studies comparing the influence of deep vs moderate NMB during laparoscopic procedures on surgical space conditions and clinical outcomes. Trials were identified from Medline, Embase, and Central databases from inception to December 2016. We included randomized trials, crossover studies, and cohort studies. Our search yielded 12 studies on the effect of deep NMB on the surgical space conditions. Deep NMB during laparoscopic surgeries improves the surgical space conditions when compared with moderate NMB, with a mean difference of 0.65 (95% confidence interval (CI): 0.47-0.83) on a scale of 1-5, and it facilitates the use of low-pressure pneumoperitoneum. Furthermore, deep NMB reduces postoperative pain scores in the postanaesthesia care unit, with a mean difference of - 0.52 (95% CI: -0.71 to - 0.32). Deep NMB improves surgical space conditions during laparoscopic surgery and reduces postoperative pain scores in the postanaesthesia care unit. Whether this leads to fewer intraoperative complications, an improved quality of recovery, or both after laparoscopic surgery should be pursued in future studies. The review methodology was specified in advance and registered at Prospero on July 27, 2016, registration number CRD42016042144.


When should "riskier" subjects be excluded from research participation?
The exclusion of potential subjects based on increased risks is a common practice in human subjects research. However, there are no guidelines to ensure that this practice is conducted in a systematic and fair way. This gap in the literature and regulation is addressed by a specific account of a "condition on inclusion risks" (CIR), a condition under which potential subjects should be excluded from research on the basis of increased risks. This account provides a general framework for assessing standard exclusions as well as more controversial ones such as the exclusion of pregnant women and women of childbearing potential from certain types of research.


[Evaluation of surgical treatment results in patients with differentiated thyroid cancer from materials in the Oncologic Institute in Gliwice].
The optimal surgical treatment for patients with differentiated thyroid carcinoma is still controversial and discussed. The aim of this study was to analyze the effectiveness of treatment in differentiated thyroid carcinoma, to establish the prognostic value of histopathological type, clinical advancement, the extent of surgery and to estimate the therapeutic benefit rate of the radical approach. The randomized group of 768 patients with differentiated thyroid carcinoma, aged between 16 to 40 (median age 44), treated in Oncology Center Institute in Gliwice between 1986 and 1997 were analyzed. They were operated in different surgical clinics in Poland. The primary total thyroidectomy was performed in 153 of patients (20%), the secondary radical operation in 474 (62%). 136 persons were operated by less radical approach. Cervical lymph node metastases were observed in 26% of patients. Distant metastases occurred in 8% of cases. 610 persons were treated with 131I. All patients were administered hormonal therapy to suppress TSH. Locoregional recurrence occurred in 7.5% of patients. Complete remission was observed in 71.5% of persons (548 patients). The influence of distant metastases lymph node metastases and tumor size on the long-term prognosis was analyzed in univariate statistic analysis. There were no differences in survival in patients with papillary and follicular carcinoma. The 10-year survival was statistically significantly longer in patients who underwent radical surgical treatment (92%) than after non-total thyroidectomy (80%). Despite the relatively high risk of surgical complications the benefits of the radical approach were significant.


Association of angiotensin-converting enzyme insertion/deletion (ACE I/D) and angiotensinogen (AGT M235T) polymorphisms with the risk of obesity in a Tunisian population.
This study aims to determine whether genetic variants in ACE I/D and AGT M235T are associated with overweight-obesity and body mass index (BMI) in a Tunisian population. We designed an age- and sex-matched case-control study. The height and weight were measured and BMI was calculated. A total of 259 overweight-obese patients and 369 healthy controls were genotyped for the ACE I/D and AGT M235T genes using polymerase chain reaction and restriction fragment length polymorphism. ACE I/D and AGT M235T genes were associated with BMI, waist circumference and overweight-obesity (p⩽0.001). In an additive model, the I and the M alleles in ACE and AGT variants, respectively, were associated with a lower BMI: -1.45 and -2.29 units, respectively. ACE I/D genotypes were associated with dyslipidemia; AGT M235T genotypes with dyslipidemia and total cholesterol. These data suggest that variations in ACE I/D and AGT M235T affect the risk of overweight-obesity, BMI and dyslipidemia, and could point to a key molecular pathway of metabolic syndrome and its related comorbidities.


Team Action Imagery and Team Cognition: Imagery of Game Situations and Required Team Actions Promotes a Functional Structure in Players' Representations of Team-Level Tactics.
A team's cognitions of interpersonally coordinated actions are a crucial component for successful team performance. Here, we present an approach to practice team action by way of imagery and examine its impact on team cognitions in long-term memory. We investigated the impact of a 4-week team action imagery intervention on futsal players' mental representations of team-level tactics. Skilled futsal players were assigned to either an imagery training group or a no imagery training control group. Participants in the imagery training group practiced four team-level tactics by imagining team actions in specific game situations for three times a week. Results revealed that the imagery training group's representations were more similar to that of an expert representation after the intervention compared with the control group. This study indicates that team action imagery training can have a significant impact on players' tactical skill representations and thus order formation in long-term memory.


Racial and ethnic disparities in infant mortality rates--60 largest U.S. cities, 1995-1998.
During the 20th century, U.S. infant mortality rates (IMRs) declined by 90%; however, many of the largest U.S. cities continue to have high IMRs compared with national rates. Studies of U.S. infant mortality by region document persisting geographic disparities and differences across racial/ethnic groups. This report highlights the wide disparities in the most recent overall race- and ethnicity-specific IMRs for the largest U.S. cities and describes key differences among those cities. The findings demonstrate the need to decrease infant mortality among blacks in U.S. cities.


Self-reported Non-celiac Gluten Sensitivity in the Korean Population: Demographic and Clinical Characteristics.
Non-celiac gluten sensitivity is characterized by intestinal and extra intestinal symptoms associated with the consumption of gluten-containing food. Since biomarkers for non-celiac gluten sensitivity are lacking, its prevalence is estimated based on self-reported symptoms. However, no data exist on self-reported non-celiac gluten sensitivity in the Korean population. Thus, we aim to investigate the prevalence of self-reported non-celiac gluten sensitivity in the Korean population and to determine its demographic and clinical characteristics. This study surveyed Korean participants aged 18-80 years who visited gastroenterology outpatient clinics at 9 tertiary hospitals in South Korea from January 2016 to February 2017. They were questioned regarding symptoms related to gluten ingestion: degree of discomfort (visual analog scale score), frequency, time of symptom onset, and duration. Abdominal discomfort caused by 11 different kinds of gluten-containing Korean food items was investigated. More non-celiac gluten sensitivity self-reporters were identified among those with irritable bowel syndrome (33.6%) than among controls (5.8%). Major gastrointestinal symptoms included bloating (75.0%), abdominal discomfort (71.3%), and belching (45.0%). Common extra-intestinal symptoms included fatigue (20.0%) and headache (13.7%). More than half of those who self-reported non-celiac gluten sensitivity (66.3%) developed symptoms within 1 hour of food ingestion, and symptoms were localized in the upper abdomen (37.5%) and entire abdomen (30.0%). Our findings suggest that if there are gluten-related symptoms in irritable bowel syndrome, the possibility of accompanying non-celiac gluten sensitivity should be considered.


Dual Fulvestrant-Trametinib Therapy in Recurrent Low-Grade Serous Ovarian Cancer.
Low-grade serous ovarian carcinoma (LGSOC) is known to exhibit chemoresistance. Effective treatment options for recurrent disease are few and often limited to hormone antagonism. Combination of endocrine therapies with MEK-inhibitors displays synergism in preclinical ovarian cancer models, however. This brief communication presents the use of combination anti-estrogenic and MEK-inhibitor therapies, fulvestrant and trametinib, as treatment in a heavily pretreated patient with estrogen receptor-positive, recurrent LGSOC. The dual-therapy regimen was well tolerated and appeared to confer 9 months of progression-free survival. Further investigation is warranted to explore this effect.


Comparative in vivo analysis of the role of the adventitia and the endothelium on arterial mechanical function: relevance for aortic counterpulsation.
The comparative effect of the intimal and adventitial layers on arterial biomechanics control, in basal and altered conditions, remains to be elucidated. This study aimed (1) to characterize the arterial conduit (CF) and buffering (distensibility) function of the iliac arteries in in vivo animals, in which the intimal and adventitial layers were removed; (2) to determine the effects of intra-aortic ballon pumping (IABP) on simultaneously de-adventitialized (DA) and de-endothelialized (DE) iliac arteries before and after induced heart failure. Pressure and diameter signals were measured in the iliac arteries of sheep (n = 7) in which the adventitial and intima layer were removed. Intra-aortic balloon pump (IABP) assistance was used in a control state and after heart failure induction. Both DE and DA determined significant changes in arterial diameter, distensibility and CF. Changes were higher after DA than after DE in terms of distensibility and CF (p<0.05). DA followed by DE (DA + DE) showed significant increases in arterial diameter and CF, accompanied by a decrease in distensibility (p<0.05) with respect to intact arteries. Heart failure induction caused significant hemodynamic changes without modifying the already impaired local biomechanical parameters. Nonsignificant improvements in the biomechanical parameters of DA + DE iliac arteries were observed during IABP before and after heart failure induction. Biomechanical changes caused by DA of iliac arteries were more important than those observed after DE. The DA + DE arteries showed significant differences with respect to intact arteries and with DA or DE arteries. IABP-related effects on arterial mechanics were absent in DA + DE arteries.


Rehabilitation of an edentulous atrophic maxilla with four unsplinted narrow diameter titanium-zirconium implants supporting an overdenture.
The edentulous maxilla is often affected by bone resorption, sometimes making it difficult to place standard diameter implants. Narrow diameter implants made of titanium-zirconium (Ti-Zr) alloy, which has superior mechanical properties compared with titanium, have been proposed for these difficult situations. This retrospective clinical observation reports the outcome of the use of reduced diameter implants made of Ti-Zr alloy supporting maxillary overdentures retained with locator abutments. The charts of all patients who received maxillary overdentures supported by four unsplinted implants from January 2009 to June 2010 at the Department of Periodontology and Prosthodontics, Eastman Dental Hospital, Rome, Italy, were reviewed. All patients treated with four narrow diameter Ti-Zr implants were selected for the present case series. Ten patients were found, six of whom received augmentation procedures. After 12 to 16 months of follow-up, no implants were lost, and only one implant showed bone resorption greater than 1.5 mm. Implants showed a success rate of 97.5% and a survival rate of 100%. All prostheses were successfully in function. The present case series showed promising results regarding the use of narrow diameter implants made of Ti-Zr supporting maxillary overdentures retained with locator abutments.


A Case of Anti-neutrophil Cytoplasmic Antibody-Associated Vasculitis Presenting With Diffuse Alveolar Hemorrhage and Renal Sparing.
Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a necrotizing vasculitis disease that traditionally includes three variants classified based on their clinical and pathological appearance: microscopic polyangiitis (MPA), granulomatosis with polyangiitis, and eosinophilic granulomatosis with polyangiitis (alternatively, Churg-Strauss syndrome). The mainstay of AAV treatment is immunosuppressive treatments, which improve survival and lower rates of end-stage kidney disease. Here we describe a patient with MPA ANCA who presented with diffuse alveolar hemorrhage and, six months later, recurrent pulmonary hemorrhage with renal sparing while off therapy.


[The effects of repetitive limb ischemia on the systemic concentration of NO, NOS in plasma of healthy humans].
To investigate the effects of RLI on plasma nitric oxide (NO) and NO synthase (NOS) isoforms of healthy humans. 30 healthy human subjects (aged from 40 - 70 years old) were recruited. RLI was induced by five 5 min cycles of ischemia of non dominant arm (200 mmHg, 5 min interval). Blood pressure, heart rate, and the feelings of ischemic arm were continuously monitored. Venous plasma was collected in contralateral arm at Pre, Post-0 h, Post-4 h, and Post-24 h. Plasma level of NO was measured by Griess reaction, and NOS was measured by chemical method. Blood pressure and heart rate varied in normal range. The uncomfortable feeling was decreased with the increasing numbers of ischemic cycles. Plasma level of NO, and iNOS in plasma were significantly increased at Post-0 h, Post-4 h, and Post-24 h compared to Pre (P < 0.05). tNOS was also significantly increased at Post-0 h and Post-4 h compared to Pre (P < 0.05). No significant change in plasma cNOS was shown at following three time points than Pre. These findings suggest that RLI can elevate plasma level of NO, tNOS, and iNOS in healthy humans. RLI might be a safe method as a rIPC, and it would have important possibility to be performed in clinic.


Examining the origins of gender differences in marital quality: a behavior genetic analysis.
Numerous researchers have examined gender differences in marital quality, with mixed results. In this study, the authors further this investigation by looking for genetic and environmental sources of variation in marital quality. The 1st aim of the study was to replicate previous findings of genetic and nonshared environmental influences on marital quality. The 2nd was to explore the etiology of gender differences in marital quality. The Virginia Adult Twin Study of Psychiatric and Substance Use Disorders sample of twin men and twin women was used. Genetic and nonshared environmental factors were again found to influence marital quality. Findings also suggest small differences between men and women in the levels of genetic and environmental influence on variance in marital quality. The men's reports of marital warmth and conflict were influenced by the same genetic factors, but women's reports of marital warmth and conflict were influenced by different genetic factors. Results are discussed in the context of previous research on social support and implications for future studies of the etiology of marital quality.


Analgesic effect of aspirin, mefenamic acid and their combination in post-operative oral surgery pain.
A double-blind randomized single dose study of the analgesic effects of 650 mg aspirin, 250 mg mefenamic acid, the combination of 650 mg aspirin and 250 mg mefenamic acid and placebo on 120 patients with pain following oral surgery was conducted. Patients evaluated their pain intensity and extent of pain relief at 1, 2, 3 and 4 h after drug administration. For most parameters, including the sum of the pain intensity differences and the sum of the hourly pain relief scores, each of the drugs was more effective than placebo. Aspirin-mefenamic acid in combination was more effective than both drugs alone, and aspirin and mefenamic acid alone were equally effective for most of the analgesic variables.


[Treatment of patients with visceral candidiasis].
To study effectiveness of antimycotic medication with flucostat in patients with visceral candidiasis. Diagnosis of bronchopulmonary, gastrointestinal, urogenital candidiasis was verified microbiologically in 152 patients aged 20 to 78 years. Candidiasis was treated with flucostat: 50 mg and 150 mg capsules per os and solution (100-50 ml) intravenously by dropper. The response was achieved in 140 (92.1%) patients: cure--in 107 (70.4%), improvement--in 33 (21.7%), mycological sanation--in 125 (82.2%) patients. Cure of chronic diseases complicated by mycotic infection is not always achieved after mycotic sanation. Some symptoms of severe chronic pathology persist and require long-term symptomatic treatment.


Peat moss Sphagnum riparium follows a circatrigintan growth rhythm in situ: A case report.
In situ growth of Sphagnum riparium Ångstr. shoots were monitored during the 2015 and 2016 growing seasons in Karelia, Russia. It was established that shoot growth rates fluctuated with a period of around 30 days, that is, showed a circatrigintan rhythm. Such rhythms from mosses have not been previously reported. Correlation of growth rates with the percentage of the illuminated portion of the Moon was statistically significant (p<0.01) in both years. Shoot growth rates were reliably higher around the new Moon compared to the full Moon. This phenomenon may be due either to causality or to a pure coincidence of processes with similar rhythms.


Stochastic resonance in biological nonlinear evolution models.
We investigate stochastic resonance in the nonlinear, one-dimensional Fisher-Eigen model (FEM), which represents an archetypal model for biological evolution based on a global coupling scheme. In doing so we consider different periodically driven fitness functions which govern the evolution of a biological phenotype population. For the case of a simple harmonic fitness function we are able to derive the exact analytic solution for the asymptotic probability density. A distinct feature of this solution is a phase lag between the driving signal and the linear response of the system. Furthermore, for more complex systems a general perturbation theory (linear response approximation) is put forward. Using the latter approach, we investigate stochastic resonance in terms of the spectral amplification measure for a quadratic, a quartic single-peaked, and for a bistable fitness function. Our analytical results are also compared with those of detailed numerical simulations. Our findings vindicate that stochastic resonance does occur in these nonlinear, globally coupled biological systems.


The Running Barbed Tie-over Dressing.
Barbed suture technology is becoming increasingly popular in plastic surgery and is now being used in body contouring surgery and facial rejuvenation. We describe the novel application of a barbed suture as a running tie-over dressing for skin grafts. The barbs act as anchors in the skin, so constant tensioning of the suture is not required. The bidirectional nature of the suture prevents any slippage, and the barbs even act as a grip on the underlying wool dressing. Furthermore, the method described is both quick and simple to learn and would be useful for the sole operator.


Microbiomes: unifying animal and plant systems through the lens of community ecology theory.
The field of microbiome research is arguably one of the fastest growing in biology. Bacteria feature prominently in studies on animal health, but fungi appear to be the more prominent functional symbionts for plants. Despite the similarities in the ecological organization and evolutionary importance of animal-bacterial and plant-fungal microbiomes, there is a general failure across disciplines to integrate the advances made in each system. Researchers studying bacterial symbionts in animals benefit from greater access to efficient sequencing pipelines and taxonomic reference databases, perhaps due to high medical and veterinary interest. However, researchers studying plant-fungal symbionts benefit from the relative tractability of fungi under laboratory conditions and ease of cultivation. Thus each system has strengths to offer, but both suffer from the lack of a common conceptual framework. We argue that community ecology best illuminates complex species interactions across space and time. In this synthesis we compare and contrast the animal-bacterial and plant-fungal microbiomes using six core theories in community ecology (i.e., succession, community assembly, metacommunities, multi-trophic interactions, disturbance, restoration). The examples and questions raised are meant to spark discussion amongst biologists and lead to the integration of these two systems, as well as more informative, manipulatory experiments on microbiomes research.


Signal transduction in hypertension: Part I.
During the past year, there has been significant progress in the knowledge of mechanisms involved in the intracellular transduction of extracellular signals. These advances have allowed a more detailed understanding of how receptors involved in contraction and relaxation of smooth muscle cells couple to intracellular effector systems and of the growth response that characterizes the behavior of blood vessels in hypertension. A large measure of this progress relates to identifying receptor subtypes of regulatory proteins that modulate activation of intracellular or membrane enzymes participating in contraction, relaxation, and growth as well as new pathways of signal transduction. Major new findings in mechanisms of cell signaling and growth in vascular smooth muscle are discussed in part I, and their involvement in hypertension are discussed in part II.


The "bringing into cultivation" phase of the plant domestication process and its contributions to in situ conservation of genetic resources in Benin.
All over the world, plant domestication is continually being carried out by local communities to support their needs for food, fibre, medicine, building materials, etc. Using participatory rapid appraisal approach, 150 households were surveyed in 5 villages selected in five ethnic groups of Benin, to investigate the local communities' motivations for plant domestication and the contributions of this process to in situ conservation of genetic resources. The results indicated differences in plant domestication between agroecological zones and among ethnic groups. People in the humid zones give priority to herbs mainly for their leaves while those in dry area prefer trees mostly for their fruits. Local communities were motivated to undertake plant domestication for foods (80% of respondents), medicinal use (40% of respondents), income generation (20% of respondents) and cultural reasons (5% of respondents). 45% of the species recorded are still at early stage in domestication and only 2% are fully domesticated. Eleven factors related to the households surveyed and to the head of the household interviewed affect farmers' decision making in domesticating plant species. There is gender influence on the domestication: Women are keen in domesticating herbs while men give priority to trees.


Effect of isosmotic removal of extracellular Ca2+ and of membrane potential on cell volume in muscle cells.
Isosmotic removal of extracellular Ca2+ (Cao) and changes in membrane potential (Vm) are frequently performed manipulations. Using isolated voltage-clamped barnacle muscle cells, we studied the effect of these manipulations on isosmotic cell volume. Replacing Cao by Mg2+ induced 1) verapamil-sensitive extracellular Na(+)-dependent membrane depolarization, 2) membrane depolarization-dependent cell volume reduction in cells whose sarcoplasmic reticulum (SR) was presumably loaded with Ca2+ [intracellular Ca2+ (Cai)-loaded cells], and 3) cell volume increase in cells whose SR was presumably depleted of Ca2+ (Cai-depleted cells) or in Cai-loaded cells whose Vm was held constant. Membrane depolarization induced 1) volume reduction in Cai-loaded cells or 2) verapamil-sensitive volume increase in Cai-depleted cells. This suggests tha, in Cai-loaded cells, membrane depolarization induces SR Ca2+ release, which in turn promotes volume reduction. Conversely, in Cai-depleted cells, the depolarization activates Na+ influx through a verapamil-sensitive pathway leading to the volume increase. This pathway is also revealed when Cao is removed in either Cai-depleted cells or in cells whose Vm is held constant.


Recent Advances in Efficacy of using Doxorubicin Gold Nanoparticles for Chemo-, Radio-, Photothermal, and Photodynamic Therapy.
Nanoparticles (NPs) have been widely used in drug delivery systems specifically for chemo-, radio-, photothermal, and photodynamic therapy. Due to the lack of selectivity toward tumor cells, the main target in therapies is to deliver drugs to cancer cells to reduce side effects. Gold nanoparticles (AuNPs) have been described as "promising nanocarriers for therapeutics" due to many properties such as low inherent toxicity, high water solubility, and biocompatibility. Many research groups have focused on taking advantage of two or more therapies simultaneously to have increased efficacy using a lower dosage of the therapeutic drug and reduced multi-drug resistance (MDR). Alternatively, doxorubicin (Dox) modification has been used as a strategy for increased selectivity toward target cells. Over the years, many studies have been performed on NPs to eliminate side effects using polymers, peptides, proteins, DNA, metallic NPs, microgels, and hydrogels on drug carriers. In this review, recent advances of using Dox-AuNPs for chemo-, radio-, photothermal, photodynamic, and combination therapy are briefly discussed, and we also highlight recent progress in the application of Dox-AuNPs for effective cancer therapy.


[Use of enalapril, an angiotensin-converting enzyme inhibitor, in pulmonary artery hypertension].
Enalapril (E) was used to treat 16 patients with pulmonary arterial hypertension, 6 primary and 10 secondary, 5 of the latter with congenital heart disease and 5 with chronic obstructive pulmonary disease. The average dose of E was 20 mg/day. All patients underwent pre and post-treatment cardiac catheterization with determination of pressures at: right atrial (RA), main pulmonary artery (MPA), pulmonary capillary wedge pressure ( VCP) and systemic arterial (SA). Resistances forces were also measured as; total pulmonary (TPR), pulmonary arteriolar (PAR) and total systemic (TSR) as well as cardiac output (CO), and echo and electrocardiograms, chest x ray, stress test and respiratory function test. The functional class (NYHA) improved in all (p less than 0.001). The initial mean pressures were: RA 12.24 +/- 4.35; MPA 73.81 +/- 25.16; VCP 12 +/- 2.73 and SA 89 +/- 14; TPR 1477 +/- 761; PAR 1243 +/- 730 and TSR 1684 +/- 505.5; CO 4.5 +/- 1.29. The final values were: RA 9.66 +/- 2.46 (p less than 0.001); MPA 63.26 +/- 24.45 (p less than 0.001); VCP 11.33 +/- 2.38 (p = NS); SA 81 +/- 10 (p less than 0.001); TPR 1009.5 +/- 536.7 (p less than 0.001); PAR 829 +/- 511.5 (p less than 0.001); TSR 1309.6 +/- 296.3 (p less than 0.001); CO 5.2 +/- 1.44 (p less than 0.001). The average of minutes on treadmill was initially 8.2 +/- 2.45 and final 12.46 +/- 3.0 (p less than 0.001). It is concluded that enalapril is a useful drug in the treatment of pulmonary arterial hypertension of any etiology.


Chain free association, creativity, and the default mode network.
Research on creativity shows that creative thinking entails both executive (controlled) and associative (spontaneous) processes. Yet standard creativity tasks cannot reliably isolate these two types of cognitive processes, making it difficult to understand the relation between the two and the roles of their corresponding brain networks in creative cognition. In this study we used a behavioral and neuroimaging approach in an effort to establish chain free association (FA) tasks as a relevant method for directly investigating spontaneous associative thinking and its role in creative cognition. We further examined the relation between performance on such tasks and intelligence. Participants completed common creativity tasks and then underwent fMRI scanning while producing FA chains. Instructions to participants that emphasized the spontaneous nature of the task, coupled with proper control conditions that were balanced for difficulty, enabled us to uncover spontaneous (as opposed to controlled) processes. To examine whether behavioral measures that can be derived from FA chains (associative fluency, associative flexibility and semantic remoteness between associations) are indicative of unconstrained spontaneous associative processing and are related to different aspects of verbal creativity and intelligence, scores on these measures were correlated with scores on creativity tasks and on an intelligence task, and with brain activity. We found that: (1) the Default Mode Network (DMN), a network involved in self-generated and internally-directed thought, was more involved in chain FA than in other tasks expected to reflect more controlled forms of internally-directed thought, suggesting that the DMN involvement might be related to the unconstrained spontaneous nature of chain FA. Higher involvement of the left IFG, SFG, MFG under chain FA was also revealed; (2) higher scores on different behavioral measures from FA chains were related to higher activation of the DMN and to reduced activation of the left IFG, a major node in the executive function network; (3) behavioral measures from FA chains were correlated with different aspects of creative performance but not with intelligence. Taken together, these findings lend support to the hypothesis that chain FA involves associative spontaneous thinking. They further suggest that behavioral measures derived from chain FA could indicate patterns of unconstrained associative thinking, related to reduced cognitive control, that are relevant for creative ideation, and might be able to serve as a measure of these patterns.


n-n* oscillations in models with large extra dimensions.
We analyze n-n* oscillations in generic models with large extra dimensions in which standard-model fields propagate and fermion wave functions have strong localization. We find that in these models n-n* oscillations might occur at levels not too far below the current limit.


Formulation, biopharmaceutical evaluation and in-vitro screening of polyherbal phytosomes for breast cancer therapy.
Saudi Arabia has a rich culture of folk medicines and three such common herbs used by Saudi people for therapy of breast cancer are Turmeric (Kurkum) Curcuma longa, Chamomile (Babunaj) Matricaria chamomilla, and Aswaghantha (Aswaghadh) Withania somnifera. Hence, the present study aims to develop a polyherbal phytosome formulation by thin film hydration technique with a synergistic anti-cancer effect for the treatment of breast cancer. The phytosomes were standardized for their phytoconstituents by HPTLC and showed the best optimal properties with a mean vesicle diameter of less than 200 nm, zeta potential in the range of -24.43 to -35.70 mV, and relatively integrated structure with fairly uniform size on TEM. The in vitro MTT assay on MCF-7 breast cancer cell lines and MDA MB 231 breast adenocarcinoma cell lines was carried out. MTT assay on MCF-7 breast cancer cell lines indicated that plant extract-loaded phytosomes exhibited enhanced cytotoxic effects at IC50 values. of 55, 50, 45, 52, 42, 44, and 20 µg/mL compared to the extracts of C. longa, M. chamomilla, W. somnifera, and their combined extracts (80, 82, 74, 60, 70, 60, and 35 µg/mL respectively). Moreover, intracellular reactive oxygen species production was found to be higher for phytosomes treated cells at respective IC50 concentrations when compared to extracts. Overall, the developed polyherbal phytosomes were found to be effective and afford synergistic effects for breast cancer therapy.


Ursolic Acid Reverses the Chemoresistance of Breast Cancer Cells to Paclitaxel by Targeting MiRNA-149-5p/MyD88.
Paclitaxel (PTX) is widely used as a front-line chemotherapy for breast cancer treatment. However, its clinical applications are limited by the development of chemoresistance. The objective of this study was to investigate the reversal effects of ursolic acid (UA) on PTX resistance and the possible mechanisms in breast cancer. The role of miRNA-149-5p/MyD88 in the regulation of PTX resistance was investigated by the transfection of breast cancer cells with MDA-MB-231 (231) and MDA-MB-231/PTX-resistance (231/PTX) with lentiviruses carrying the MyD88 gene, shRNA specific for MyD88, the miR-149-5p gene, and shRNA specific for miR-149-5p. The PTX sensitivity was assessed by a CCK-8 assay. qRT-PCR and Western blot analyses were used to detect changes in the mRNA and protein levels. Flow cytometry was used to measure the rate of cell apoptosis. A luciferase activity assay was used to detect the binding site of miR-149-5p on the 3'UTR of MyD88. 231/PTX cells were injected into the flanks of female athymic nude mice, and the mice were randomly divided into the five following groups: PBS, PTX (low), PTX (high), UA, and PTX+UA. Our data show that UA reversed the resistance of breast cancer 231/PTX cells to PTX in vitro and in vivo. UA treatment significantly increased the expression of miR-149-5p, which was lower in 231/PTX cells than in 231 cells. Furthermore, the overexpression of miR-149-5p increased the sensitivity of 231/PTX cells to PTX treatment, whereas the knockdown of the miR-149-5p gene attenuated the effects of UA on the regulation of PTX sensitivity. A luciferase assay demonstrated that miR-149-5p could directly regulate the transcriptional activity of MyD88, a known PTX-resistance gene, by targeting the 3'UTR of MyD88. Meanwhile, the downregulation of MyD88 through the overexpression of miR-149-5p or UA treatment inhibited the activation of the Akt signaling pathway in 231/PTX cells. Thus, our data indicate that UA can reverse PTX resistance by targeting the miRNA-149-5p/MyD88 axis in breast cancer cells.


Glycoprotein-enriched vesicles from sheep erythrocyte ghosts obtained by spontaneous vesiculation.
Sheep erythrocyte membranes have been shown in this laboratory to undergo spontaneous vesiculation when incubated at 4 degrees, fractionating into two bands in dextran gradients (R. McGuire and R. Barber, submitted for publication). While vesicles were observed to be formed in several solvent systems, incubation in the presence of complexors to remove divalent cations was found to be the most efficient method for both vesicle formation and their detachment from the residual membrane. We report here on the characterization of these vesicles formed by spontaneous vesiculation. In the presence of a hypotnoic buffer containing 1 mM EDTA, vesicle production proceeds linearly up to 50 hours and declines, reaching its maximum at 72 hours with up to 20% of the total membrane protein found in the upper band. This upper band is shown in electron micrographs to be composed chiefly of closed vesicles, while the particles in the lower band appear morphologically similar to the original ghosts. Total phospholipid phosphorus and cholesterol in the vesicles are enriched to the same extent, giving a lipid to protein ratio of 2 times that found for whole ghosts. The vesicles contain the same individual phospholipids as the ghosts. The protein composition of these vesicles is unique, in that they are almost depleted in the known extrinsic membrane proteins, while containing practically all types of the various glycoproteins of the original membrane. The two main intrinsic membrane proteins (with apparent molecular weights of 160,000 and 100,000) are found almost exclusively in the vesicles, virtually depleted in the residual ghost-like particles. The protein with 160,000 molecular weight is shown here to be a glycoprotein, giving an anomalous molecular weight on sodium dodecyl sulfate gels and having a molecular weight of approximately 50,000 after lipid extraction. This same glycoprotein appears to fractionate with acetylcholinesterase. From the accessibilities of the substrates to the membrane acetylcholinesterase and NADH-diaphorase, it is concluded that the vesicles are right-side-out and sealed to small molecules. There are more membrane sialic acid residues accessible to neuraminidase in the vesicles (in terms of number of residues/mg og membrane protein) than in ghosts, further supporting the conclustion that these vesicles have a normal orientation and are enriched in glycoproteins. The specific activity of acetylcholinesterase in the vesicles is increased 5- to 6-fold over that found in the original ghosts and almost 20-fold over that in the residual ghost-like particles. Consequently, spontaneous vesiculation occurs simultaneously with the enrichement of specific membrane proteins in certain regions of the lipid bilayer. It is postulated that these domains in the membrane, containing clusters of specific intrinsic membrane proteins, bud out and subsequently release glycoprotein-enriched lipid vesicles.


Phase dependencies of the human baroreceptor reflex.
We studied the influence of respiratory and cardiac phase on responses of the cardiac pacemaker to brief (0.35-s) increases of carotid baroreceptor afferent traffic provoked by neck suction in seven healthy young adult subjects. Cardiac responses to neck suction were measured indirectly from electrocardiographic changes of heart period. Our results show that it is possible to separate the influences of respiratory and cardiac phases at the onset of a neck suction impulse by a product of two factors: one depending only on the respiratory phase and one depending only on the cardiac phase. This result is consistent with the hypothesis that efferent vagal activity is a function of afferent baroreceptor activity, whereas respiratory neurons modulate that medullary throughput independent of the cardiac phase. Furthermore, we have shown that stimulus broadening and stimulus cropping influence the outcome of neck suction experiments in a way that makes it virtually impossible to obtain information on the phase dependency of the cardiac pacemaker's sensitivity to vagal stimulation without accurate knowledge of the functional shape of stimulus broadening.


Chromosome 17 In Situ Hybridization Grid-based Analysis in Oral Squamous Cell Carcinoma.
Oral squamous cell carcinoma (OSCC) is an aggressive malignancy due to its increased ability for local metastases and distant lymph node metastases. Extensive cytogenetic analyses have detected chromosome instability (CI) patterns in OSCC including gross chromosome numerical alterations, such as polysomy and sporadically monosomy that negatively affect the biological behaviour of the malignancy. Our aim was to investigate the frequency and impact of chromosome 17 (Chr 17) numerical imbalances in OSCC. Fifty (n=50) formalin-fixed, paraffin-embedded primary OSCCs tissue sections were used. Chromogenic in situ hybridization (CISH) was implemented for detecting Chr 17 centromeric numerical imbalances. Concerning the screening process in CISH slides, a novel real-time reference and calibration grid platform was implemented. Chr 17 multiple copies were observed in 12/50 (24%) of the examined cases. Polysomy was observed in 10/50 (20%) tissue sections, monosomy in 2/50 (4%), whereas the rest of them demonstrated a normal, diploid pattern (38/50-76%). Chr 17 numerical differences were associated with the grade of differentiation of the examined tumors (p=0.001). Chr 17 numerical imbalances (polysomy predominantly and monosomy) are observed in sub-groups of OSCCs correlating with a progressive dedifferentiation of malignant tissues. The proposed grid-based platform on CISH slides provides a novel, fast and accurate screening-mapping mechanism for detecting chromosome numerical aberrations.


A Case of "Abnormally Abnormal" Hypoxic Ventilatory Responses: A Novel NPARM PHOX 2B Gene Mutation.
Congenital central hypoventilation syndrome (CCHS) is a rare disorder associated with dysregulation of the autonomic ventilatory response to hypoxia and hypercarbia usually caused by polyalanine repeat expansion mutations in the PHOX 2B gene. Non-polyalanine repeat mutations (NPARM) represent approximately 10% of cases, and usually require continuous ventilation during sleep, although our knowledge of disease progression is limited. Here we present a case with a novel NPARM CCHS mutation associated with a premature stop codon for the PHOX 2B protein. Despite the type of the mutation, patient management with supplementary oxygen has been sufficient. Experience from our case may help when counseling parents.


Rabies Cases in the West of China Have Two Distinct Origins.
In China, rabies remains an ongoing threat to public health. Although control efforts have been effective in reducing the number of annual cases, the virus continues to spread into new areas. Tibet, Qinghai, Gansu and Ningxia in western China have, until recently, reported only a handful of events. However, since 2011, there have been increasing numbers of cases recorded in these areas. In this study, we report the collection and analysis of samples collected from these regions. We find that cases originate from two different sources. Strains collected from Gansu and Ningxia are closely related to the primary lineage associated with the current epizootic, whereas those from Tibet and Qinghai are related to the Arctic-like-2 lineage that is most commonly associated with wildlife cases in China. Thus, it appears that while the epizootic is beginning to encroach into Gansu and Ningxia, Tibet and Qinghai a significant number of rabies cases originate from wildlife.


Further localization of the gene for nevoid basal cell carcinoma syndrome (NBCCS) in 15 Australasian families: linkage and loss of heterozygosity.
Nevoid basal cell carcinoma syndrome (NBCCS; basal cell nevus syndrome or Gorlin syndrome) is a cancer-predisposition syndrome characterized by multiple basal cell carcinomas (BCCs) and diverse developmental defects. The gene for NBCCS has been mapped to 9q23.1-q31 in North American and European families. In addition, loss of heterozygosity (LOH) for genetic markers in this region has been detected in sporadic BCCs, indicating that the NBCCS gene is probably a tumor-suppressor gene. In this study we have determined that the NBCCS gene is also linked to this region in Australasian pedigrees and that there is no significant evidence of heterogeneity. We have defined the localization of the gene by multipoint and haplotype analysis of 15 families, using four microsatellite markers. LOH at these loci was detected in 50% of sporadic BCCs, a rate that is significantly higher than that in other skin lesions used as controls.


Up-regulation of the human prolactin receptor in the endometrium.
In humans, uterine endometrial stromal cells differentiate (decidualize) into decidual cells that express prolactin (PRL). Decidual PRL expression continues throughout pregnancy, thus decidual cells lining fetal membranes of term placenta synthesize and secrete PRL. To examine the hypothesis that PRL may play an autocrine role in the decidual cells, we examined the expression of the PRL receptor (PRL-R) during in vitro decidualization of stromal cells and in term decidua. In endometrial stromal cells decidualized by treatment with 1 μM medroxyprogesterone and 10 nM estradiol for 3, 6, and 9 d, respectively, a 12.7 kb PRL-R transcript increased 3-3.5-fold, 16.5-17-fold, and 23.5-24-fold, respectively, compared with untreated controls, in duplicate experiments. Progesterone-dependent PRL-R and PRL expression were stimulated by 1 μ/M prostaglandin E(2). Term decidua expressed the long form of the PRL-R and five major PRL-R transcripts (12.7, 9.7, 7.0, 3.6, and 2.8 kb). In contrast, human liver expressed two major transcripts (12.7 and 9.7 kb) while hepG2 cells expressed a single 7.0-kb-sized transcript. These studies demonstrate that PRL-R expression is stimulated upon progesterone-induced PRL gene expression in endometrial stromal cells supporting the hypothesis that PRL may have an autocrine effect in the endometrium and decidua.


Interpersonal cognitive biases as genetic markers for pediatric depressive symptoms: twin data from the emotions, cognitions, heredity and outcome (ECHO) study.
Childhood depressive symptoms may arise from genetic and environmental risks, which act to bias the ways in which children process emotional information. Previous studies show that several "cognitive biases" are heritable and share genetic and environmental risks with depressive symptoms. Past research suggests that many cognitive biases only reflect genetic risks for depressive symptoms from adolescence. The present study sought to identify (a) when interpersonal cognitions mature as risk factors for depressive symptoms by examining whether these factors are stable and predict symptoms across time in childhood, and (b) the extent to which interpersonal cognitions reflect inherited/environmental risks on children's depressive symptoms. Results showed that there was some stability for interpersonal cognitive biases from age 8 to 10 years (rs = .32-.43). Only the absence of positive self/other perceptions, and negative peer and mother expectations at age 8 predicted depressive symptoms at age 10 (after controlling for depressive symptoms at age 8). The absence of positive self/other perceptions shared genetic influences with depressive symptoms within and across time. Across middle to late childhood, interpersonal cognitions begin to operate as vulnerability-trait factors for depressive symptoms, gradually reflecting distal genetic risks on symptoms.


A passive haemagglutination test for rabies antibodies using rabies glycoprotein coupled erythrocytes.
The presently recommended tests for assaying rabies antibodies like mouse neutralization test (MINT) and rapid fluorescent focus inhibition test (RFFIT) are either time consuming or expensive and are generally performed in reference laboratories. There is a need to develop a specific and rapid method for detection of rabies antibodies that can be used to monitor sero-conversion after pre-or post-exposure vaccination. In this study, we have developed a passive haemagglutination (PHA) using purified rabies virus glycoprotein coupled to sheep erythrocytes using chromium chloride (0.04%) as a coupling agent. Two hundred and fifty five serum samples from people vaccinated with different rabies vaccines, 16 paired serum and CSF samples from autopsy confirmed cases of paralytic rabies, and serum samples from 65 normal healthy controls were tested and evaluated in comparison to standard MNT. Among the vaccinees, 250 samples were positive both by MNT and PHA but 5 samples were negative by PHA and positive by MNT. The titres obtained by PHA were lower compared to MNT, but there was significant correlation between the two (r=0.885). The specificity of the test was 99.7% and sensitivity was 100% as compared to MNT. Thus this PHA test promises to be a rapid and specific test for assaying rabies antibodies and may be useful in screening large number of serum samples for sero conversion after vaccination. It may also assist in rapid laboratory confirmation of paralytic rabies cases, based on detection of antibodies in CSF and serum.


Recombinant hemopoietic growth factors. Molecular cloning and potential therapeutic applications.
In analogy with data obtained from other mammalian species it appears that the majority of physiologically relevant human hemopoietic growth factors (e.g. erythropoietin and colony stimulating factors) has been characterized in biological systems, defined by biochemical methods and manufactured by molecular cloning of the corresponding genetic elements and expression in suitable biological systems. A review of the present situation of production of recombinant hemopoietic growth factors is presented and potential therapeutic applications of these factors will be discussed. In addition some preliminary clinical results, due to the medical application of recombinant hemopoietic growth factors, will be described.


Does isolated teratozoospermia affect performance in in-vitro fertilization and embryo transfer?
The effect of the strict classification of spermatozoal morphology on the outcome of in-vitro fertilization and embryo transfer treatment cycles has been assessed in a retrospective analysis of 2144 consecutive cycles. The patients all had a standardized long protocol gonadotrophin-releasing hormone analogue cycle, with luteal phase start, to achieve down-regulation. All treatment cycles where the sperm density was abnormal (< 20 x 10(6)/ml), or where progressive motility was abnormal (< 40%), were excluded. The study excluded treatment cycles where the oocytes inseminated did not include at least one grade 1 or grade 2 oocyte. The percentage of couples achieving the normalized results of the clinic, including median fertilization rate per patient, insemination rates, numbers of embryos transferred, rates of 'spare embryo' blastocyst formation, cumulative pregnancy rates and pregnancy outcome, were calculated. No statistically significant difference arose between the two groups of patients with regard to the percentage of patients achieving the normalized median fertilization rate or higher (group 1 with > 14% normal forms, and group 2 with > or = 4%, < or = 14% normal forms). There was a statistically significantly lower chance of achieving this rate in patients of group 3 (< 4% normal forms) (P < 0.005), but 68.6% did achieve that fertilization rate or higher. There was no statistically significant difference in any of the other end points. In conclusion, a morphological classification may be appropriate as an indicator for counselling patients with regard to treatment expectations, but its use would be seem inappropriate as an index of fertilizing potential in clinical management.(ABSTRACT TRUNCATED AT 250 WORDS)


Prolonged survival of microencapsulated neonatal porcine islets in mice treated with a combination of anti-CD154 and anti-LFA-1 monoclonal antibodies.
The aim of this study was to determine whether short-term administration of a combination of anti-CD154 and anti-LFA-1 monoclonal antibodies can prolong the survival of microencapsulated neonatal porcine islets (NPI) in immunocompetent mice. Microencapsulated NPI were transplanted into the peritoneal cavity of streptozotocin-induced diabetic B6 mice that received a short-term treatment of a combination of anti-CD154 and anti-LFA-1 monoclonal antibodies. Blood glucose levels of each recipient were measured for more than 100 days posttransplantation or until graft rejection. Microcapsules were recovered to determine the presence of immune cells using immunoperoxidase staining. In addition, the levels of mouse anti-porcine immunoglobulin (Ig) G antibodies in the serum of each recipient were measured by flow cytometry. Short-term administration of a combination of monoclonal antibodies resulted in significant prolongation of microencapsulated NPI xenograft survival. All treated mice (n = 20) achieved normoglycemia within 10-35 days posttransplantation and 11/20 mice remained normoglycemic for more than 100 days posttransplantation. In contrast, only 1/20 of the untreated mice achieved normoglycemia and this mouse became diabetic at 17 days posttransplantation. Histological examination of the recovered microcapsules from long-term surviving treated mice revealed minimal cellular overgrowth containing intact viable islets, whereas several layers of immune cells surrounding the capsules containing nonviable islets were observed in untreated mice. The levels of mouse anti-porcine IgG was also reduced in treated recipients compared to untreated mice. These data demonstrate that short-term administration of anti-CD154 and anti-LFA-1 monoclonal antibodies can be effective in promoting long-term survival of microencapsulated NPI in immune-competent mice.


Addictions Neuroclinical Assessment: A reverse translational approach.
Incentive salience, negative emotionality, and executive function are functional domains that are etiologic in the initiation and progression of addictive disorders, having been implicated in humans with addictive disorders and in animal models of addictions. Measures of these three neuroscience-based functional domains can capture much of the effects of inheritance and early exposures that lead to trait vulnerability shared across different addictive disorders. For specific addictive disorders, these measures can be supplemented by agent specific measures such as those that access pharmacodynamic and pharmacokinetic variation attributable to agent-specific gatekeeper molecules including receptors and drug-metabolizing enzymes. Herein, we focus on the translation and reverse translation of knowledge derived from animal models of addiction to the human condition via measures of neurobiological processes that are orthologous in animals and humans, and that are shared in addictions to different agents. Based on preclinical data and human studies, measures of these domains in a general framework of an Addictions Neuroclinical Assessment (ANA) can transform the assessment and nosology of addictive disorders, and can be informative for staging disease progression. We consider next steps and challenges for implementation of ANA in clinical care and research. This article is part of the Special Issue entitled "Alcoholism".


Electrical and Optical Properties of Si-Incorporated a-C:H Films via the Radio Frequency Plasma-Enhanced Chemical Vapor Deposition Method.
The optical and electrical properties of silicon-incorporated hydrogenated amorphous carbon (a-C:H:Si) films deposited via the radio frequency (RF) plasma-enhanced chemical vapor deposition (PECVD) method using a mixture of CH4, H2, and SiH4 were observed. The silane gas whose ranged from 0 to 25 vol.% [SiH4/(SiH4 + CH4) was fed into the reactor while the other deposition parameters were kept constant. The basic properties of these films were investigated via Raman spectroscopy, UV-visible spectrometry, I-V measurement, and surface profiling. The experiment results showed that the film thickness increased from 300 nm to 800 nm for the same deposition time as the silane gas increased. The Raman spectrum obtained from the silicon-incorporated a-C:H films suggested that the film property changed from graphitic-like to more diamond-like. As the silane gas increased, the optical gap, E04, slightly increased from 1.98 eV to 2.62 eV. It was shown that the Si atoms incorporated into the a-C:H films reduced the size of the sp2 clusters. As for the I-V characteristics, the Si-incorporated a-C:H films had a lower leakage current than the a-C:H films without Si.


A Metascientific Review of the Evidential Value of Acceptance and Commitment Therapy for Depression.
In the past three-and-a-half decades, nearly 500 randomized controlled trials (RCTs) have examined Acceptance and Commitment Therapy (ACT) for a range of health problems, including depression. However, emerging concerns regarding the replicability of scientific findings across psychology and mental health treatment outcome research highlight a need to re-examine the strength of evidence for treatment efficacy. Therefore, we conducted a metascientific review of the evidential value of ACT in treating depression. Whereas reporting accuracy was generally high across all trials, we found important differences in evidential value metrics corresponding to the types of control conditions used. RCTs of ACT compared to weaker controls (e.g., no treatment, waitlist) were well-powered, with sample sizes appropriate for detecting plausible effect sizes. They typically yielded stronger Bayesian evidence for (and larger posterior estimates of) ACT efficacy, though there was some evidence of significance inflation among these effects. RCTs of ACT against stronger controls (e.g., other psychotherapies), meanwhile, were poorly powered, designed to detect implausibly large effect sizes, and yielded ambiguous-if not contradicting-Bayesian evidence and estimates of efficacy. Although our review supports a view of ACT as efficacious for treating depression compared to weaker controls, future RCTs must provide more transparent reporting with larger groups of participants to properly assess the difference between ACT and competitor treatments such as behavioral activation and other forms of cognitive behavioral therapy. Clinicians and health organizations should reassess the use of ACT for depression if costs and resources are higher than for other efficacious treatments. Clinical trials contributing effects to our synthesis can be found at https://osf.io/qky35.


Interactions Between the Gastrointestinal Microbiome and Clostridium difficile.
Antibiotics have significant and long-lasting effects on the intestinal microbiota and consequently reduce colonization resistance against pathogens, including Clostridium difficile. By altering the community structure of the gut microbiome, antibiotics alter the intestinal metabolome, which includes both host- and microbe-derived metabolites. The mechanisms by which antibiotics reduce colonization resistance against C. difficile are unknown yet important for development of preventative and therapeutic approaches against this pathogen. This review focuses on how antibiotics alter the structure of the gut microbiota and how this alters microbial metabolism in the intestine. Interactions between gut microbial products and C. difficile spore germination, growth, and toxin production are discussed. New bacterial therapies to restore changes in bacteria-driven intestinal metabolism following antibiotics will have important applications for treatment and prevention of C. difficile infection.


Incidence, characteristics, and outcome of left atrial tachycardias after circumferential antral ablation of atrial fibrillation.
Antral pulmonary vein isolation (PVI) for treatment of atrial fibrillation may induce left atrial tachycardias (ATs). To determine the prevalence, time course of occurrence, mechanisms, and correlation with the electrocardiogram as well as the outcome of ablation of these tachycardias. Out of the 839 patients who underwent circumferential antral radiofrequency PVI guided by a circumferential pulmonary vein catheter at our institution between February 2005 and April 2011, 35 patients (4%) developed AT during follow-up. Six patients with left AT and a previous PVI at other institutions were also included. Of these 41 patients (26 men, 63%; age 59 ± 10 years), 26 (63%) had underlying paroxysmal atrial fibrillation and 15 (37%) had persistent atrial fibrillation. AT ablation was performed 47 ± 60 weeks after initial PVI, within the first 3 months in 16 patients (39%). The tachycardia mechanism was focal in 15 patients (37%), macroreentry in 25 patients (61%), and undetermined in 1 (2%). Focal tachycardias had an isoelectric line between distinct P waves in 13 of the 15 patients (87%), while only 4 (16%) with a macroreentrant mechanism had an isoelectric line (P <.001). Although difficult to measure, a P-wave width of >140 ms had the highest sensitivity and specificity to identify macroreentrant mechanism. Ablation was acutely successful in 32 patients (78%) and not successful in 4 (10%). In 5 patients, success could not be determined as the tachycardia terminated or degenerated during mapping. During a mean follow-up of 31 ± 17 months, 11 patients (27%; n = 9 [82%] with macroreentry) underwent repeat ablation procedure for AT. Eight patients had true recurrence, for example, the same AT, and 3 patients had a second mechanism of AT. With the use of an identical ablation protocol, it was found that approximately 4% of the patients developed AT after mere circumferential antral PVI. The majority of ATs developed within a few months after ablation but occurred as late as several years after the initial PVI. Macroreentry was more frequent than a focal mechanism. Broad P waves and isoelectric lines between P waves help to distinguish a focal mechanism from a macroreentrant mechanism. Ablation has a high acute success rate, and AT recurrence occurs predominantly in macroreentrant AT.


A glomus tumour involving the base of the skull.
The glomus tumours can invade considerable areas of the base of the skull with no presenting symptoms or if any they can hardly be guiding. The diagnosis in most of the cases is made 5 to 8 years after the onset of the disease. Operative treatment may be efficient, but depends on the operability of the case. In our case of an inoperable glomus tumour involving the middle and posterior cranial fossae, tinnitus appeared as an initial symptom. A week later peripheral facial palsy developed. On the 15th day the patient's deglutition was impaired. At the end of the fifth month bleeding from the ear appeared. Otoscopy of the outer ear showed an irregular, granular formation in the anterior quadrants. The biopsy proved alveolar paraganglioma. The size of the tumour was evaluated with computerized tomography with and without contrast medium and digital subtraction angiography. We report the case because of the long latent asymptomatic course of the disease with penetration in the skull base. The first symptoms, manifested at the inoperable stage, was suggestive of involvement of the middle and inner ear.